Various cosmetic preparations are on the market which are intended for the whitening of skin and which are also intended to prevent the formation of skin spots. These comprise a variety of components, part of which are synthetic products and which may have deleterious side effects. The activity of such preparations varies and in some cases a very slight effect is obtained, if at all. The present invention provides an improved cosmetic skin whitening composition with enhanced efficacy.
The present invention relates to novel cosmetic composition for topical application which result in whitening of the skin and which prevent to a large extent further formation of skin spots.
The composition of the invention comprise in combination extracts of the root of Glycyrrhiza glabra or associated species in a powder form which contain approx. 10% of glabridine which are effective in reducing melanin synthesis by inhibiting tyrosinase activity, together with alpha or beta hydroxy or keto acids.
Each component mentioned in this invention demonstrates effectiveness in fade-out of human skin spots. When the components are blended they produce a significant increase (p-value 0.01) in tyrosinase inhibitory activity. This activity was greater than the sum of the inhibitory activity of each of the components alone.
It seems, based on tests we have performed, that the synergistic effects are also due to the fact that alpha or beta hydroxy acids or a keto acid, their esters as well as inorganic or organic salts, such as glycolic acid, Citric acid, Lactic acid, Malic acid, Tartronic acid, Tartaric acid, Glucoronic acid, Pyruvic acid, 2-hydroxy isobutyric acid, Ethyl or Methyl pyruvate when applied topically in a concentration between 0.5% and 30% decrease corneocytes cohesion which results in reducing thickness of the stratum corneum and therefore increasing penetration of the active ingredients.
Plant extracts which can be used are for example, from six varieties of glycyrrhiza glabra Linne, Glycyrrhiza uralensis Fisher, Glycyrrhiza inflator Batalin or associated species from the Leguminosae family of plants.
The product is extracted from the root of the plant. 1 kg of the root from Licorice is mixed with 10 liters of anhydrous ethanol and heated under reflux for 5 hours. The decoction is collected and concentrated under reduced pressure. To this extract 1 liter of ethyl acetate is added and heated under reflux for 5 hours. The filtrate is concentrated under reduced pressure and dried. Yellow to red powder is obtained.
Generally the compositions will contain from about 0.005% wt to about 5% wt of the dried plant extract, the preferred range being between 0.05%-0.2%.
Amongst the a-hydroxy, .beta.-hydroxy, or keto acids, their organic or inorganic salts or esters are: glycolic acid, lactic acid, malic acid, citric acid, Pyruvic acid, Tartaric acid, Salicylic acid, etc.,
The quantity of alpha or beta hydroxy or keto acid used in the compositions will vary between about 0.1% to about 30% the preferred range being from about 1% to about 8%.
Amongst optional ingredients of such skin whitening compositions there may be mentioned sun filter in the UVA & UVB range, vitamins or their derivatives, such as Vitamin C or E.
Extensive experiments have demonstrated that the cosmetic compositions of the invention result in an effective skin whitening, and it is believed that this is due to the synergistic activity of the mixed ingredients on the inhibition of tyrosinase, which normally converts tyrosine to melanin.
Furthermore, by reducing stratum corneum thickness, this synergistic effect is enhanced.
Test in vitro on the effect of glycolic acid and glycyrrhiza dry extract on tyrosinase inhibitory activity has been carried out based on the Methodology of Maruzene Pharmaceuticals. The anti-tyrosinase activity was investigated by colorimeter comparison at 475 nm and calculated as percentage of the inhibitory activities. (Attached are the results).
TABLE 1 ______________________________________ In vitro tyrosinase inhibitory activity of Glycolic acid Glycolic acid concentration % Tyrosinase Inhibition % Tyrosinase Inhibition mg/5 ml. Test 1. Test 2. ______________________________________ 7.21 10.74 27.81 1.61 7.60 21.32 0.805 5.64 16.11 0.42 4.86 9.12 ______________________________________
TABLE 3 ______________________________________ In vitro tyrosinase inhibitory activity of Leguminosae species extract with Glycolic acid Glycolic Leguminosae species acid conc. ext. conc. Test 1 Test 2 mg/5 ml. mg/5 ml. a b a b ______________________________________ 7.21 0.04 39.23 63.28 60.45 70.02 1.61 0.04 36.09 60.03 53.96 66.85 0.805 0.04 34.13 55.44 48.75 60.41 0.42 0.04 33.35 53.73 41.76 48.94 ______________________________________ a Theoretical inhibitory activity Sum of % inhibition of Leguminosae species extract and different concentrations of Glycolic acid. b In vitro % inhibitory activity of the combination of Leguminosae specie extract and Glycolic acid.
TABLE 2 ______________________________________ In vitro tyrosinase inhibitory activity of Leguminosae species extract Leguminosae species % Tyrosinase % Tyrosinase extract Inhibition Inhibition mg/5 ml. Test 1. Test 2. ______________________________________ 0.04 28.49 32.64 0.02 11.74 19.94 0.01 8.67 16.48 0.005 5.18 12.70 ______________________________________
The following results of experiments carried out with human volunteers are representative of a series of experiments. These are by way of illustration only and are not to be construed in a limitative manner.
Test on human volunteers was conducted according to HRL protocol.
In the following examples the quantities are in weight-%. All designations are according to CTFA names.
Example 1: Cream PA0 Example 2: Cream
______________________________________ Licorice extract 0.15 Cream base, up to 100.00 ______________________________________
The effect is one of inhibition of tyrosinase activity, which converts tyrosin to melanin.
______________________________________ Licorice extract 0.15 Glycolic acid 8.00 Cream base, up to 100.00 ______________________________________